Stimulation of Human CD4+ T Lymphocytes via TLR3, TLR5 and TLR7/8 Up-Regulates Expression of Costimulatory and Modulates Proliferation

The cells of innate and adaptive immunity, although activated by different ligands, engage in cross talk to ensure a successful immune outcome. Toll-like receptors (TLRs) are key components of the innate immune system and have the ability to detect microbial infection and trigger host defence responses. Otherwise, human T lymphocytes are able to produce most TLRs. Thus, we analyze the capability of some TLR ligands to modulate the function of highly-purified CD4+ T cells. We found that agents acting via TLRs (poly I:C, a TLR3 ligand; flagellin, a TLR5 ligand; and R848, a TLR7/8 ligand) are able to regulate the expression of costimulatory molecules both on purified antigen presenting cells and on purified T lymphocytes. Moreover, the activation mediated by TLRs determines a kinetic expression of B7-family members such as through an inhibition of T lymphocytes delayed proliferation. These findings suggest a functional role of some invading microorganisms in regulating acquired immunity

Anti-DFS70 antibodies detected by specific methods in patients with thrombosis or recurrent pregnancy loss: no evidence of an association

A dense fine speckled pattern (DFS) caused by antibodies to the DFS70 kDa nuclear protein is a relatively common finding while testing for anti-nuclear antibodies (ANA) by indirect immunofluorescence (IIF) on HEp-2 cells. However, despite many efforts and numerous studies, the clinical significance of anti-DFS70 antibodies is still unknown as they can be found in patients with various disorders and even in healthy subjects. In this study we aimed at verifying whether these antibodies are associated with thrombotic events or with unexplained recurrent pregnancy loss (RPL). We studied 443 patients with venous or arterial thrombosis or RPL and 244 controls by IIF on HEp-2 cells and by a DFS70-specific chemiluminescent immunoassay (CIA). The DFS pattern was observed in IIF in 31/443 (7.0%) patients and in 6/244 (2.5%) controls (p\u2009=\u20090.01) while anti-DFS70 specific antibodies were detected by CIA in 11 (2.5%) patients and in one (0.4%) control (p\u2009=\u20090.06). Positive samples, either by IIF or by CIA, were then assayed by a second DFS70-specific line-immunoassay (LIA) method: 83.3% of the CIA positive samples were confirmed DFS70 positive versus only 29.7% of the IIF positive samples. These findings show that IIF overestimates anti-DFS70 antibody frequency and that results obtained by specific CIA and LIA assays do not indicate that venous or arterial thrombosis or RPL are linked to a higher prevalence of anti-DFS70 antibodies

The Role of CTLA-4 Gene Polymorphisms in Autoimmune Disease Pathogenesis: A 2012 Update

Gene association studies are very appealing in autoimmune diseases. In recent years, access to other human gene sequences prompted investigators to focus on genes encoding the immune regulatory proteins such as the costimulatory, adhesion molecules, cytokines and chemokines and their receptors. Among them, cytotoxic T-lymphocyte antigen-4 (CTLA-4) has been extensively studied for its pivotal role in autoimmunity. As a central regulatory element of the immune responses magnitude, CTLA-4 could act as a double-edged sword and only the optimal expression ensures an effective, but at the same time, safe immune response. Thus, we can argue that CTLA-4 alleles associated with abnormal membrane expression could make a person more susceptible to tumor growth and/or manifestation of autoimmune diseases. Unfortunately, the relationship between the presence of SNP conferring susceptibility/protection to autoimmune disease and the genetic regulation/modification of CTLA-4 is the not yet fully clarified, and in some aspects conflicting

The inhibitory co-receptors: a way to save from anergy the HIV-specific T cells.

The functional impairment of HIV-specific CD4(+) T cells during chronic HIV infection is thought to be closely linked to viral replication and to T cell exhaustion. T cell exhaustion in the presence of ongoing antigen exposure is a common feature of chronic viral infection, in which dysfunctional T cells fail to eliminate the virus. Otherwise, antiviral T cell function impairment is a poorly understood mechanism. Increasing evidences show that HIV-specific T lymphocytes up-regulated inducible co-receptors, such as the Cytoxic T Lymphocyte Antigen-4, (CTLA-4, or CD152) and Programmed Death-1 (PD-1) and that blockade of the CD152 or PD-1 pathway restores HIV-specific CD4(+) T cell function in HIV infection. This review will focus on finding a possible role for inhibitory receptors on virus-specific CD4(+) T cells. The analysis of the role of CD152 and PD-1 in HIV-1 infection could provide important insight into the mechanism of viral induced immune dysfunction and lead to immunotherapeutic strategies to reverse immune suppression in this pathology

The Anatomia Universa (1823) of Paolo Mascagni (1755–1815): The memory of a masterpiece in the history of anatomy after two centuries

Two hundred years ago, the first of the nine volumes of Paolo Mascagni's Anatomia universa was published posthumously. This work was the fruit of a project that preoccupied Mascagni for most of his life: the Atlas of anatomy, which was the perfect replica on paper of the dissection, a fundamental part of the teaching of this discipline.Mascagni's treatises testify to the modernity of his approach to medical education, and his deep conviction that the main objective was to educate young people and to enable them to acquire the most perfect knowledge of the structure of the human body

Oversecretion of soluble CTLA-4 in various autoimmune diseases overlapping celiac disease.

Aim: To evaluate the levels of soluble CTLA-4 (s CTLA-4) in sera of celiac disease (CD) patients with overlapping autoimmune diseases (OAD; diabetes mellitus, autoimmune thyroid diseases, inflammatory bowel diseases, and autoimmune polyendocrine syndromes). Methods: Sera from Italian patients with CD were obtained and enzyme-linked immunosorbent assay (ELISA) was used to measure sCTLA-4. Results: Consistently high serum sCTLA-4 levels were observed in CD (13.20 ng/ml, p < 0.0001), and OAD (19.48 ng/ml, p < 0.0001) compared to normal controls. A significant increase in the level of serum sCTLA-4 was observed in OAD (p = 0.0273) compared to CD alone. At variance, no significant difference in the sCTLA-4 levels was observed when single overlapping autoimmune diseases were compared. Conclusion: The present study shows for the first time a statistically significant increase of serum sCTLA-4 levels in CD patients with associated autoimmune disease (namely, CD and OAD) vs. patients with CD alone. Previously, the potential genetic associations of several CTLA-4 polymorphisms to susceptibility to autoimmune diseases have been described, although the relationship between CTLA-4 polymorphisms and the ability to produce the soluble form is not fully clarified. CTLA-4 is a strong actor in the adaptive response: our data give supportive evidence of the common background of autoimmune diseases